Unique biosynthesis of dehydroquinic acid?

A search of the genomic sequences of the thermophilic microorganisms Aquifex aeolicus, Archaeoglobus fulgidus, Methanobacterium thermoautotrophicum, and Methanococcus jannaschii for the first seven enzymes (aroG, B, D, E, K, A, and C ) involved in the shikimic acid biosynthetic pathway reveal two key enzymes are missing. The first enzyme in the pathway, 3-deoxy-d-arabino-heptulosonic acid 7-phosphate synthase (aroG) and the second enzyme in the pathway, 5-dehydroquinic acid synthase (aroB) are "missing." The remaining five genes for the shikimate pathway in these organism are present and are similar to the corresponding Escherichia coli genes. The genomic sequences of the thermophiles Pyrococcus abyssi and Thermotoga maritima contain the aroG and aroB genes. Several fungi such as Aspergillus fumigatus, Aspergillus nidulans, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pneumocystis carinii f. sp. carinii, and Neurospora crassa contain the gene aroM, a pentafunctional enzyme whose overall activity is equivalent to the combined catalytic activities of proteins expressed by aroB, D, E, K, and A genes. Two of these fungi also lack an aroG gene. A discussion of potential reasons for these missing enzymes is presented.     

What makes the bioactive lipids phosphatidic acid and lysophosphatidic acid so special?

Phosphatidic acid and lysophosphatidic acid are minor but important anionic bioactive lipids involved in a number of key cellular processes, yet these molecules have a simple phosphate headgroup. To find out what is so special about these lipids, we determined the ionization behavior of phosphatidic acid (PA) and lysophosphatidic acid (LPA) in extended (flat) mixed lipid bilayers using magic angle spinning 31P NMR. Our data show two surprising results. First, despite identical phosphomonoester headgroups, LPA carries more negative charge than PA when present in a phosphatidylcholine bilayer. Dehydroxy-LPA [1-oleoyl-3-(phosphoryl)propanediol] behaves in a manner identical to that of PA, indicating that the difference in negative charge between LPA and PA is caused by the hydroxyl on the glycerol backbone of LPA and its interaction with the phosphomonoester headgroup. Second, deprotonation of phosphatidic acid and lysophosphatidic acid was found to be strongly stimulated by the inclusion of phosphatidylethanolamine in the bilayer, indicating that lipid headgroup charge depends on local lipid composition and will vary between the different subcellular locations of (L)PA. Our findings can be understood in terms of a hydrogen bond formed within the phosphomonoester headgroup of (L)PA and its destabilization by competing intra- or intermolecular hydrogen bonds. We propose that this hydrogen bonding property of (L)PA is involved in the various cellular functions of these lipids.     

Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability?

Experimental animal and human studies have indicated that long chain polyunsaturated fatty acids (LCPUFA) may enhance calcium absorption, reduce urinary calcium excretion, and increase bone calcium content. In the present study, the effect of LCPUFA, as provided in evening primrose oil, fish and tuna oils, on calcium bioavailability was investigated. Growing male rats were fed a semi-synthetic diet for 6 weeks, after which calcium absorption, bone mineral density (ex vivo), bone calcium content, and bone biomechanics were measured. Calcium absorption, ex vivo bone mineral density, and bone calcium content were significantly higher in the animals fed tuna oil compared with those of a control group fed corn oil. Significant correlations were found between the docosahexaenoic acid (DHA) (22:6n-3) content of the red cell membranes and bone density and bone calcium content. DHA increased accretion of calcium in bone significantly more so than eicosapentaenoic acid (EPA) (20:5n-3).     

Pantothenic acid supplementation to support rumen microbes?

Based on repeatedly reported extensive pantothenic acid disappearance in the rumen, the present study is aimed at examining if pantothenic acid is used for a more efficient ruminal fermentation and microbial growth in an artificial rumen (Rusitec). Three substrates differing in roughage/concentrate ratio were incubated with and without the addition of Ca-D-pantothenate. Pantothenic acid was extensively degraded without notably influencing fermentation, microbial protein synthesis and the status of other B-vitamins such as riboflavin, vitamin B6 and niacin. Therefore, pantothenic acid supplementation cannot be expected to contribute to microbial benefit for the ruminant animal.     

Understanding gibberellic acid signaling--are we there yet?

The phytohormone gibberellic acid (GA) controls important aspects of plant growth such as seed germination, elongation growth, and flowering. The key components of the GA signaling pathway have been identified over the past 10 years. The current view is that GA binds to a soluble GID1 receptor, which interacts with the DELLA repressor proteins in a GA-dependent manner and thereby induces DELLA protein degradation via the E3 ubiquitin ligase SCF(GID2/SLY1). GA-dependent growth responses can generally be correlated with and be explained by changes in DELLA repressor abundance, where the DELLA repressor exerts a growth restraint that is relieved upon its degradation. However, it is obvious that other mechanisms must exist that control the activity of this pathway. This review discusses recent advances in the understanding of GA signaling, of its homeostasis, and of its cross-talk with other signaling pathways.     

Too much linoleic acid promotes inflammation-doesn't it?

Controversy exists over how much linoleic acid (LA) should be consumed in a healthy diet. Some claim that high LA intake promotes inflammation through accumulation of tissue arachidonic acid (AA) and subsequent production of pro-inflammatory lipid mediators. Here the author reviews the current available evidence from human studies that address this issue. The data indicate that high LA in the diet or circulation is not associated with higher in vivo or ex vivo pro-inflammatory responses. Surprisingly, several studies showed that those individuals consuming the highest level of LA had the lowest inflammatory status. Recent findings suggest that LA and AA are involved in both pro- and anti-inflammatory signaling pathways. Thus, within the ranges of intake that are achievable for most human populations, the evidence do not support reducing LA intake below current consumption levels.     

Citric acid as a siderophore of enterococci?

In the pool of 70 enterococcal strains of the genus Enterococcus 61.4% released citrate into the medium. This metabolite has occurred more frequently in E. faecium strains. There was no correlation between hydroxamate siderophores production and citrate releasing. Only nine (10, 3%) of 70 strains have used Fe3+-dicitrate complex as iron sources. Iron restricted condition causing moderate inhibition of growth have not increased citrate releasing. When iron deficiency has caused stronger growth inhibition, E. faecalis strains did not release citrate and E. faecium strains its smaller amounts. The resting cells grown in iron-restricted condition have incorporated 59Fe3+ complexed by citrate more active than cells grown in the medium with excess of iron. So, citrate has not been a siderophore in enterococci.     

How does ascorbic acid prevent endothelial dysfunction?

Human coronary and peripheral arteries show endothelial dysfunction in a variety of conditions, including atherosclerosis, hypercholesterolemia, smoking, and hypertension. This dysfunction manifests as a loss of endothelium-dependent vasodilation to acetylcholine infusion or sheer stress, and is typically associated with decreased generation of nitric oxide (NO) by the endothelium. Vitamin C, or ascorbic acid, when acutely infused or chronically ingested, improves the defective endothelium-dependent vasodilation present in these clinical conditions. The mechanism of the ascorbic acid effect is unknown, although it has been attributed to an antioxidant function of the vitamin to enhance the synthesis or prevent the breakdown of NO. In this review, multiple mechanisms are considered that might account for the ability of ascorbate to preserve NO. These include ascorbate-induced decreases in low-density lipoprotein (LDL) oxidation, scavenging of intracellular superoxide, release of NO from circulating or tissue S-nitrosothiols, direct reduction of nitrite to NO, and activation of either endothelial NO synthase or smooth muscle guanylate cyclase. The ability of ascorbic acid supplements to enhance defective endothelial function in human diseases provides a rationale for use of such supplements in these conditions. However, it is first necessary to determine which of the many plausible mechanisms account for the effect, and to ensure that undesirable toxic effects are not present.     

Arachidonic acid cytotoxicity: can arachidonic acid be a physiological mediator of cell death?

Arachidonic acid is a polyunsaturated fatty acid that mediates inflammation and the functioning of several organs and systems either directly or upon its conversion into eicosanoids. However, arachidonic acid is found to be cytotoxic in vitro at concentrations that overlap physiological ones. It is tempting therefore to speculate that arachidonic acid may be a physiological inducer of apoptosis and that such cytotoxic action may be another of its roles in vivo. Nevertheless its pro-inflammatory and oxidative stress-inducing features are characteristic of necrosis and pathological conditions. We hereby review the cytotoxic action of arachidonic acid, indicate the possible pathways that lead to cell death and contemplate the cytotoxic role of arachidonic acid in vivo.     

Is retinoic acid genetic machinery a chordate innovation?

Development of many chordate features depends on retinoic acid (RA). Because the action of RA during development seems to be restricted to chordates, it had been previously proposed that the "invention" of RA genetic machinery, including RA-binding nuclear hormone receptors (Rars), and the RA-synthesizing and RA-degrading enzymes Aldh1a (Raldh) and Cyp26, respectively, was an important step for the origin of developmental mechanisms leading to the chordate body plan. We tested this hypothesis by conducting an exhaustive survey of the RA machinery in genomic databases for twelve deuterostomes. We reconstructed the evolution of these genes in deuterostomes and showed for the first time that RA genetic machinery--that is Aldh1a, Cyp26, and Rar orthologs--is present in nonchordate deuterostomes. This finding implies that RA genetic machinery was already present during early deuterostome evolution, and therefore, is not a chordate innovation. This new evolutionary viewpoint argues against the hypothesis that the acquisition of gene families underlying RA metabolism and signaling was a key event for the origin of chordates. We propose a new hypothesis in which lineage-specific duplication and loss of RA machinery genes could be related to the morphological radiation of deuterostomes.